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From the Radheshyam Kanoi Stem Cell Laboratory (SP, SK) and the Larson & Toubro Department of Ocular Pathology (SK), Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Vision Research Foundation, Chennai, India; and Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, India (VK). The authors have no financial or proprietary interest in the materials presented herein. Correspondence: Vikas Khetan, MD, Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India. E-mail: [email protected] doi:10.3928/01913913-20171116-01 Of the organ systems, the nervous system is the first to initiate and last to complete. The neural system of a child undergoes tremendous development, with more than 2,500 synapses per neuron at birth that increase to 15,000 synapses per neuron by age 3 years. Proper functioning of the neural circuit requires not only the production of nerve cells, which are the building blocks of the nervous system, but also detailed guidance to locations that result in their making appropriate connections. The neurons have a cell body with extensions called axons and dendrites. Whereas dendrites are smaller and branched, axons are longer and single. The neural circuit functions only when the axon of one neuron makes a long-lasting and faithful connection (synapse) with the dendrite of the other. The selection of the axon and dendrite partners for the synaptic connection is not straightforward or random; it is the result of an educated sequence of trial and error attempts of the axons and dendrites to connect to each other correctly. In bilaterally symmetric animals, the information processed from the left and right halves of the central nervous system (CNS) must be integrated for proper cognition and motor function. This requires some of the nerves from one half of the CNS to cross the midline and connect to the other half. The precision of the neural connections depends largely on the leading edge of the axon, referred to as the “growth cone,” which bestows the axons with the impetus to navigate over long distances in response to guidance molecules released in the local environment. The accuracy of axon crossing at the midline is dependent on the guidance of secreted molecules that attract (chemoattractant) and repel (chemorepellent) the axons. These chemoattractant and chemorepellent proteins are produced by the combination of a ligand and an axonal cone receptor of the ligand (in biochemistry, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose). One of the predominant guidance signaling complexes at the midline is the SLIT-ROBO pathway, with SLIT being the ligand and the axon’s roundabout guidance (ROBO) reThe Roundabout Way of Finding the Right Target